Human herpesviruses are responsible for a variety of clinically signficant diseases which, under certain circumstances, can be life threatening. Available genetic and biochemical evidence suggests that HSV encodes most, if not all, of the proteins which are either directly or indirectly involved in viral DNA synthesis. The genetic studies proposed herein are designed to identify viral genes involved in HSV-1 DNA synthesis through the isolation and characterization of a series of isogenic host range, null and other mutants of HSV-1. The availability of a series of mutants derived from a single wild-type strain of HSV-1 which are altered in their ability to carry out DNA synthesis will be important in identifying viral gene products required for DNA replication in vivo. While some viral gene products involved in DNA synthesis may not be essential for lytic replication, it is likely that many will play roles in the pathogenicity of the virus, perhaps in the establishment and maintenence of latent infection. It is anticipated that the mutants isolated as part of this study will facilitate the identification of viral gene products essential for establishment of and reactivation from the latent state. Preliminary biochemical and genetic evidence suggests the existence of a "viral DNA replication complex" comprised of several elements. The genetic studies proposed herein are designed to verify the existence of such a complex and to identify its components. Once gene products required for DNA synthesis are identified by the proposed genetic studies, biochemical experiments designed to elucidate their functions will be initiated. It is anticipated that the availability of HSV-1 mutants in essential and nonessential viral replication genes will not only serve to further our understanding of HSV DNA synthesis, but will also identify viral enzymes as potential targets of antiviral chemotherapy.